Feasibility and optimal imaging time window for intraperitoneal versus intravenous injection of a macrocyclic gadolinium-based contrast agent in mice

Abstract

Objective

This study aimed to evaluate the feasibility of intraperitoneal injection as an alternative to the technically challenging intravenous route for contrast agent administration in murine brain magnetic resonance imaging by comparing their enhancement effects. Specifically, it sought to determine the optimal injection dose and imaging time window for administration of gadobutrol, a macrocyclic gadolinium-based contrast agent, in orthotopic glioblastoma models.

Methods

This study used an orthotopic glioblastoma model established in BALB/c nude mice (n = 24) by intracranial implantation of LN229 cells. Mice were randomized to receive gadobutrol at doses of 1 or 2 mmol/kg via both intravenous and intraperitoneal routes on separate days. Contrast-enhanced magnetic resonance imaging was performed at multiple post-injection time points. The resulting images were evaluated qualitatively by blinded neuroradiologists and quantitatively by measuring signal-to-noise ratio and contrast-to-noise ratio, with statistical comparisons made between injection methods and dosage groups.

Results

Image quality assessments revealed no significant differences in signal-to-noise ratio, contrast-to-noise ratio, or enhancement metrics between the intravenous and intraperitoneal routes. Peak enhancement occurred at 7 min following intravenous injection and 30 min following intraperitoneal injection.

Conclusions

Intraperitoneal injection is a viable alternative, with scanning at 30 min recommended for optimal contrast enhancement.

Keywords

Contrast-enhanced magnetic resonance imaging mouse intraperitoneal injection intravenous injection dosage

Introduction

Gadolinium (Gd)-based contrast agents (GBCAs) have been used in contrast-enhanced magnetic resonance imaging (MRI) (CE-MRI) since the 1980s to characterize pathophysiological processes and diagnose diseases in humans.¹ Under physiological conditions, GBCAs barely cross the intact blood–brain barrier (BBB); therefore, enhancement in CE-MRI is typically limited to blood vessels and the pituitary gland.² In the presence of brain lesions, however, disruption or absence of the BBB may result in abnormal contrast enhancement, enabling the localization and characterization of intracranial pathologies.² Consequently, CE-MRI has become an essential tool for the diagnosis of intracranial lesions.³

For CE-MRI examinations in both humans and animals, GBCAs are typically administered intravenously, a straightforward procedure in humans and large animals.⁴ In small animals such as mice and rats, however, intravenous (IV) administration is considerably more challenging.⁵ The lateral tail vein is the most common site for IV injection in mice; however, successful injection requires precise localization of the vein, accurate dosage control, and often multiple attempts.^6,7 These technical demands not only increase procedure time but also pose limitations for longitudinal, dynamic, or high-throughput studies, as repeated IV injections may lead to vessel sclerosis.⁵ Consequently, alternative administration routes that reduce technical barriers and maintain imaging efficacy have been actively explored.⁸

As a common drug delivery route in mice, intraperitoneal (IP) injection bypasses the need for venous access, offering a simpler and more reproducible approach that is particularly attractive for preclinical imaging studies requiring repeated contrast administration.⁵ Unlike IV injection, IP injection relies on absorption through the numerous capillaries in the parietal peritoneum, after which the contrast agent enters the systemic circulation after first passing through the portal vein and liver.⁹ Previous studies have investigated the optimal injection dose and imaging time window for central nervous system (CNS) CE-MRI using intraperitoneal administration of gadoteridol, a macrocyclic GBCA.¹⁰ However, the optimal injection dose and imaging time window for gadobutrol, a high-concentration macrocyclic GBCA, in murine orthotopic glioblastoma (GBM) models remain undetermined. Therefore, this study aimed to compare the enhancement characteristics of IV and IP injection methods and to evaluate the feasibility of IP contrast administration as a practical alternative to IV administration in BALB/c nude mice.

Materials and methods

Cell culture

The human GBM cell line (LN229, ATCC CRL-2611, RRID: CVCL_0393) was initially obtained from the Type Culture Collection of the Chinese Academy of Sciences. The cell line was maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin at 37°C in 5% CO₂.

Animals

A total of 24 female BALB/c nude mice (4–5 weeks old; median weight, 16 g) were procured from Charles River Laboratories (Beijing, China). Mice were housed in sterile, individually ventilated cages under a 12-h light/dark cycle with controlled temperature (22 ± 2°C) and humidity (50% ± 10%) and had free access to autoclaved food and water. Environmental enrichment included nesting material and a shelter. All animal procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (eighth edition) and were approved by the Animal Ethical Committee (Approval Number: 2020059; Approval Date: 14 November 2020). All efforts were made to minimize the number of animals used and their suffering in accordance with the 3R principles.

After acclimatization, 4 μL of phosphate-buffered saline (PBS) containing 2 × 10⁵ LN229 cells in the logarithmic growth phase was stereotactically injected into the right striatum (1 mm posterior to the coronal suture, 2 mm lateral to the sagittal suture, and 4 mm deep) of the mice.¹¹ The 24 mice were randomly assigned to two dose groups (n = 12 per group): group 1 received 1 mmol/kg gadobutrol (1.0 mol/L, Gadovist^®, Bayer Healthcare, Leverkusen, Germany), and group 2 received 2 mmol/kg gadobutrol.⁸ Using a microsyringe, gadobutrol was administered at volumes ranging from 15 to 40 μL, depending on individual body weight to achieve the target doses. Tumor size was monitored using MRI every 5 days.

Inclusion criteria were successful tumor implantation confirmed by MRI on day 25. Exclusion criteria (established a priori) were death before completion of MRI scans, failure to achieve successful IV or IP injection after three attempts, or technical failure of MRI. Humane endpoints included loss of >20% body weight, inability to ambulate, or severe neurological signs (seizures and lethargy). No mice reached these endpoints before the scheduled MRI examinations.

Based on prior experimental experience and monitored results, LN229 cells typically form moderately sized orthotopic GBM tumors approximately 25 days after implantation. Therefore, all mice first underwent CE-MRI following IV injection on day 25 post-implantation. To minimize bias arising from potential lesion variability between animals, each mouse served as its own control. After adequate contrast agent washout, the same animal received the same dose via IP injection on day 26 post-implantation. This within-subject design ensured that comparisons between IV and IP administration were not confounded by inter-animal differences in tumor size or enhancement patterns. Mice were anesthetized with isoflurane (4%–5% for induction and 1%–2% for maintenance) during orthotopic GBM model establishment and all MRI examinations.

This study was designed as a feasibility pilot study to compare two administration routes (IP vs. IV) and two doses (1 and 2 mmol/kg) of gadobutrol. Each mouse served as its own control, with precontrast images acquired before each injection. A separate negative control group (e.g. saline injection) was not included because the primary objective was to assess whether IP injection produces enhancement comparable to that achieved with the standard IV route, rather than to evaluate absolute contrast efficacy. The absence of a negative control group is consistent with Animal research: Reporting of In Vivo Experiments (ARRIVE) guidelines for pilot feasibility studies. At the end of the experiment, mice were euthanized by cervical dislocation under deep isoflurane anesthesia. Death was confirmed by the absence of heartbeat and respiration.

Injection protocol

Intraperitoneal (Ip) injection

Mice were first restrained by grasping the dorsal skin and tail and positioned supine with the head tilted downward. The lower left abdominal quadrant was subsequently disinfected with 75% ethanol. A 0.5 mL syringe fitted with a 28-gauge needle (BD Biosciences, USA) was used to administer gadobutrol. The needle was inserted at a 30°–45° angle near the ventral midline, and correct placement was confirmed by negative aspiration (no blood or fluid return) and the absence of resistance during injection. The injection volume of gadobutrol solution was calculated using the following formula:

Injection volume (µL) = (dose in mmol/kg) × (body weight in kg)/(concentration of stock solution, 1.0 mol/L)

This calculation typically resulted in an injection volume of 15–40 µL per mouse.

Intravenous (IV) injection (tail vein injection)

Mice were restrained using a commercial mouse restrainer (Braintree Scientific, USA), and the tail vein was dilated using warm water (approximately 40 °C for 2 min). The lateral tail veins were selected for injection, avoiding the thinner dorsal vein. Following disinfection with 75% ethanol, a 28-gauge insulin syringe (0.5 mL, BD Biosciences) with the bevel facing upward was inserted into the distal tail vein stabilized at a 15° angle. Successful venous access was confirmed by smooth plunger depression without resistance or subcutaneous fluid accumulation. If unsuccessful, the procedure was repeated at a more proximal site. After injection, hemostasis was achieved by applying manual pressure for 30–60 s.

MRI protocol

MRI examinations were performed on a 3.0-T MRI system (Achieva 3.0 T TX, Philips Healthcare; Amsterdam, The Netherlands) using a 5-cm-diameter, 8-channel mouse quadrature coil. T1-weighted images (T1WIs) were obtained using the following sequence and parameters:

T1WI turbo spin echo (TSE): echo time (TE) = 9.3 ms, repetition time (TR) = 515 ms, field of view (FOV) = 40 mm (anterior–posterior (AP)) × 40 mm (right–left (RL)) × 18 mm (foot–head (FH)), voxel = 0.3 mm × 0.4 mm × 1 mm, number of signal averages (NSA) = 5, FA = 90°.

The sequence was performed before contrast injection and at eight postcontrast time points (3.5, 7, 15, 30, 45, 60, 90, and 120 min) after IV or IP injection of gadobutrol.

Qualitative assessment

All images were independently evaluated by two neuroradiologists with more than 7 years of experience in CE-MRI interpretation. All images were randomized and anonymized before scoring. The neuroradiologists were blinded to contrast agent dose, injection method, and postcontrast time points. Overall assessment of the image quality was evaluated based on three aspects: (a) border delineation, (b) internal morphology, and (c) contrast enhancement. Each aspect was scored from 1 to 4 (Table 1), and the scores from the three aspects were summed to obtain a total score, which was subsequently categorized into four levels: 3–6, “none”; 7–8, “moderate”; 9–10, “good”; and 11–12, “excellent.”

Table 1.

Qualitative analysis scoring system.

Score	Border delineation	Internal morphology	Contrast enhancement
1	No or unclear delineation	No display of the lesion structure and interior features	No enhancement
2	Some areas of clear delineation but not all	Poor display of the lesion structure and interior features	Weakly enhanced
3	Almost clear but not complete delineation	Partial display of the lesion structure and interior features	Clearly enhanced
4	Border outline is sharp with clear delineation	Lesion is well seen and complex heterogeneous areas can be seen	Clearly and brightly enhanced

Quantitative assessment

A radiologist performed all measurements of signal intensity (SI) within the regions of interest (ROIs). As shown in Figure 1, ROIs were placed within the tumor, contralateral normal white matter, and surrounding air. The delineated ROI contours were also transferred to images from different scans of the same mouse. The area of each ROI was 0.5 mm². Each ROI was measured three times, and the mean value was used to calculate the following indices: normalized SI in lesions, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), contrast enhancement, and lesion to brain ratio (LBR). These indices were calculated with the following formulas:

Normalized signal intensity = {SI}_{lesion} / S I_{white matter}

Figure 1.

Representative ROIs used for quantitative analysis on coronal CE-T1WIs of a mouse with orthotopic GBM. (a) IV injection at a dose of 1 mmol/kg; (b) IV injection at a dose of 2 mmol/kg. ROI 1 was placed within the tumor area, avoiding cystic or necrotic regions. ROI 2 was placed in the contralateral normal white matter (centrum semiovale). ROI 3 was placed in the surrounding air (outside the head) to measure the SD of background noise. All ROIs had an area of 0.5  mm² and were manually drawn by a radiologist. The same contour shapes were subsequently transferred to corresponding slices of the same mouse at different time points.

$SNR = {SI}_{lesion} / S D_{air}$

$CNR = ({SI}_{lesion} – S I_{white matter}) / S D_{air}$

$Contrast enhancement = ({SI}_{lesion post} – S I_{lesion pre}) / S I_{lesion pre}$

$LBR = ({SI}_{lesion} – S I_{white matter}) / S I_{white matter}$

The SI _lesion, SI _{white matter}, SI _{lesion pre}, and SI _{lesion post} represent the mean signal intensity of the tumor, contralateral white matter, tumor before enhancement, and tumor after enhancement, respectively. SD_air represents the mean SD of the noise measured in air.

Statistical analysis

Weighted kappa statistics were calculated to assess interobserver agreement in image evaluation for the IP and IV injection groups. The interpretation criteria were as follows: kappa values <0.20 indicated positive but poor agreement, 0.21–0.40 indicated fair agreement, 0.41–0.60 indicated moderate agreement, 0.61–0.80 indicated good agreement, and >0.81 indicated excellent agreement. Overall image quality between IV and IP injections at each dose was compared using exact multinomial tests.

Sample size was determined by power analysis based on preliminary data (expected effect size d = 1.2, α = 0.05, power = 0.8), which indicated that 12 mice per group were sufficient. Statistical analyses of SNR, CNR, contrast enhancement, and LBR were performed using Statistical Package for the Social Sciences (SPSS) software (version 25.0; IBM Corporation; Armonk, NY, USA). The Shapiro–Wilk test was used to assess normality. For normally distributed data (expressed as mean ± SD), differences between IV and IP injection groups or between the 1 and 2 mmol/kg dose groups were evaluated using two-tailed Student’s t-tests and paired-samples t-tests. For non-normally distributed data (expressed as median (quartile)), statistical analysis was performed using the Mann–Whitney U test. A p value <0.05 was considered statistically significant.

Results

Qualitative analysis

Qualitative image assessment was performed independently by two neuroradiologists blinded to dose, injection route, and imaging time point. Each image was scored for three aspects: border delineation, internal morphology, and contrast enhancement (1–4 points per aspect; total score: 3–12; levels: 3–6, “none”; 7–8, “moderate”; 9–10, “good”; and 11–12, “excellent”). Detailed individual scores for all 24 mice (12 per dose group) are provided in Table S1.

At the standard dose (1 mmol/kg), the mean total scores (sum of the three aspects) for IV and IP images were 9.25 ± 1.36 (range: 7–12) and 9.33 ± 1.60 (range: 5–11), respectively, corresponding to “good” image quality (p = 0.340). At the higher dose (2 mmol/kg), the mean total scores for IV and IP images were 9.83 ± 1.34 (range: 8–12) and 9.42 ± 1.80 (range: 5–12), respectively, also corresponding to “good” image quality (p = 0.411). The proportion of images for which IP was rated as “better” or “equal” compared with IV ranged from 66.7% to 75.0% across the two doses and the two radiologists (Table 2). The overall image quality between IV and IP at each dose was compared using exact multinomial tests, which showed no significant differences (1 mmol/kg: p = 0.423; 2 mmol/kg: p = 0.992; Table 2). Inter-rater agreement was good (κ = 0.610).

Table 2.

Overall assessment of the quality of images among different injections and dosages.

Radiologist	n	1 mmol/kg			p value	2 mmol/kg			p value
Radiologist	n	IV better (%)	IP better (%)	No difference (%)	p value	IV better (%)	IP better (%)	No difference (%)	p value
1	12	3 (25.0)	3 (25.0)	6 (50.0)	0.423	4 (33.3)	5 (41.7)	3 (25.0)	0.992
2	12	4 (33.3)	3 (25.0)	5 (41.7)	0.423	3 (25.0)	4 (33.3)	5 (41.7)	0.992

IP: intraperitoneal; IV: intravenous.

Both injection methods met the diagnostic requirements for detecting intracranial tumors in mice at the standard dose (1 mmol/kg). Throughout the experiment, no mouse showed signs of pain, distress, abnormal behavior, or local reactions (swelling, redness, or infection) at the injection site. Body weight remained stable in all groups (Figure 2), with no significant differences between the two dose groups at any time point (p > 0.05), indicating that neither dose of gadobutrol caused detectable systemic toxicity. Two mice died from an anesthetic accident after the final MRI scan. Their data were included in all analyses because all scans had been completed.

Figure 2.

Body weight changes in mice during the experimental period. Mice were divided into two dose groups: 1 mmol/kg (n = 12) and 2 mmol/kg (n = 12). No significant differences in body weight were observed between the two dose groups at any time point (p > 0.05, unpaired t-test).

Quantitative analysis

The orthotopic GBM model was used to evaluate the in vivo MRI characteristics of brain tumors. Following gadobutrol injection, the tumors showed heterogeneous and marked enhancement on T1WI, and signal enhancement changed dynamically over time (Figure 3). After IV injection, tumor enhancement became visible as early as 3.5 min, peaked at 7 min, and then gradually declined. However, after IP injection, enhancement appeared later, peaked at 30 min, and remained visible for a longer period. The higher dose (2 mmol/kg) produced visibly stronger enhancement than the standard dose (1 mmol/kg), regardless of the injection route.

Figure 3.

Representative coronal T1WI of an orthotopic GBM-bearing mouse before (0 min) and at various time points after IV or IP injection of gadobutrol at doses of 1 and 2 mmol/kg. Images were acquired at 3.5, 7, 15, 30, 45, 60, 90, and 120 min post-injection. White arrows represents tumor enhancement.

All subsequent quantitative comparisons were performed at these respective peak time points unless otherwise stated. At the time of peak enhancement, there were no significant differences between IV and IP administration for any metric (SNR, CNR, contrast enhancement, or LBR) at either dose (all p > 0.05; Figure 4, Table 3). At the 2 mmol/kg dose, the SNR, CNR, contrast enhancement, and LBR values on T1WI were significantly higher than those at the 1 mmol/kg dose at peak enhancement (p < 0.001; Figure 4, Table 4), irrespective of the injection route. At later time points (e.g. 120 min), no significant differences between doses were observed. For both routes, all quantitative metrics gradually declined after the peak. The SNR, CNR, and LBR values at 120 min after injection were close to those of the precontrast images (p > 0.05), indicating that lesion enhancement had essentially resolved by approximately 2 h, regardless of the injection route. The complete dataset, including individual animal values at all time points for SNR, CNR, contrast enhancement, and LBR, is provided in Table S2. Two mice died from anesthetic complications after the final MRI scan. Their data were included in all analyses because the scans had been completed. No adverse effects related to IP injection were observed in any mice.

Figure 4.

Quantitative comparison of image enhancement metrics between IV and IP injection of gadobutrol at doses of 1 and 2 mmol/kg. (a) SNR, (b) CNR, (c) contrast enhancement, and (d) LBR. Data are presented as mean ± SD (n = 12 per dose group). For each dose, the time to peak enhancement was 7 min for IV injection and 30 min for IP injection; these time points are shown in the figure. At the same dose, no significant differences were observed between IV and IP injection for any metric (all p > 0.05, unpaired t-test or Mann–Whitney U test, as appropriate). The 2 mmol/kg dose produced significantly higher values for all four metrics compared with the 1 mmol/kg dose at the respective peak times (***p < 0.001), regardless of injection route. Error bars represent SDs.

Table 3.

Quantitative image quality parameters (SNR, CNR, contrast enhancement, and LBR) for IV (at 7 min) and IP (at 30 min) injections of gadobutrol at doses of 1 and 2 mmol/kg.

	1 mmol/kg		p value	2 mmol/kg		p value
	IV	IP	p value	IV	IP	p value
SNR	65.43 ± 1.94	61.52 ± 1.46	0.351	90.00 ± 1.62	86.79 ± 2.99	0.793
CNR	38.89 ± 3.21	36.32 ± 2.07	0.473	45.73 ± 2.59	43.86 ± 2.55	0.971
Contrast enhancement	0.86 ± 0.08	0.85 ± 0.10	>0.999	1.13 ± 0.13	1.11 ± 0.12	>0.999
LBR	0.65 ± 0.04	0.70 ± 0.06	0.949	0.78 ± 0.05	0.87 ± 0.07	0.064

CNR: contrast-to-noise ratio; IP: intraperitoneal; IV: intravenous; LBR: lesion to brain ratio; SNR: signal-to-noise ratio.

Table 4.

Quantitative image quality parameters (SNR, CNR, contrast enhancement, and LBR) for doses of 1 and 2 mmol/kg through IV (at 7 min) and IP (at 30 min) injections of gadobutrol.

	IV		p value	IP		p value
	1 mmol/kg	2 mmol/kg	p value	IV	IP	p value
SNR	65.43 ± 1.94	90.00 ± 1.62	<0.001	61.52 ± 1.46	86.79 ± 2.99	<0.001
CNR	38.89 ± 3.21	45.73 ± 2.59	<0.001	36.32 ± 2.07	43.86 ± 2.55	<0.001
Contrast enhancement	0.86 ± 0.08	1.13 ± 0.13	<0.001	0.85 ± 0.10	1.11 ± 0.12	<0.001
LBR	0.65 ± 0.04	0.78 ± 0.05	<0.001	0.70 ± 0.06	0.87 ± 0.07	<0.001

CNR: contrast-to-noise ratio; IP: intraperitoneal; IV: intravenous; LBR: lesion to brain ratio; SNR: signal-to-noise ratio.

Discussion

In the present study, although both IP and IV injections could almost completely clear lesion enhancement within 120 min, the time to peak enhancement following IP injection was later than that following IV injection, and the rate of enhancement decline was slower. The two injection methods demonstrated no significant differences in relative signal intensities across doses, indicating that IP injection may serve as an alternative route for GBCA administration. Our findings are consistent with those of Tessier et al.,¹² who demonstrated that IP administration of gadolinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (Gd-DOTA) in healthy mice resulted in sustained brain accumulation for 2 h, as validated by mass spectrometry. Although their study focused on the intact BBB and glymphatic transport, our work in a glioma model showed peak enhancement at 30 min, followed by gradual washout, reflecting BBB disruption in tumors. Together, these complementary studies confirm that IP injection is a reliable and practical route for longitudinal brain MRI in mice, regardless of whether the BBB is intact or compromised.

Heckl et al.¹³ used 2.5 mmol/kg gadolinium diethylenetriaminepenta acetic Acid (Gd-DTPA) for CE-MRI of the spine in rats and observed maximum enhancement at 15 min after IP injection. Portnoy reported that IP administration of gadoteridol (a macrocyclic GBCA) at doses >2.5 mmol/kg produced enhancement comparable to that achieved with IV administration,¹⁰ and maximum enhancement was achieved 10–20 min after IP injection. In our study, however, the dose associated with maximum enhancement was 2 mmol/kg, and the most appropriate scanning times were 7 min after IV injection and 30 min after IP injection. These differences among studies may be attributable to variations in GBCAs, as each agent exhibits a unique in vivo distribution pattern, or to differences in the lesions across tissues, organs, and systems. In addition, the delivery pathway of GBCAs following IP administration remains unclear and requires further investigation.

There was no significant difference between the standard (1 mmol/kg) and double (2 mmol/kg) doses in either qualitative or quantitative analyses. The results of the present study are consistent with previous findings showing that 1 mmol/kg high-concentration gadobutrol is effective for steady-state MRI enhancement.⁸ Both doses of gadobutrol were well tolerated, and no unexpected safety findings were observed. This finding is consistent with the previously reported safety profile and pharmacokinetic data of gadobutrol.¹⁴

In the present study, no adverse effects (e.g. local reactions, abnormal behavior, or weight loss) were observed in any mouse following IP injection of gadobutrol, consistent with the well-established safety profile of macrocyclic GBCAs.¹⁴ Previous studies in rats have also reported that IP administration of various GBCAs does not induce nephrogenic systemic fibrosis or other systemic toxicity,¹⁵ supporting the biosafety of the IP route for preclinical imaging. Importantly, our findings demonstrated that the standard dose (1 mmol/kg) of gadobutrol provided diagnostically acceptable image quality via IP injection, without the need for a higher dose. Therefore, we recommend using the standard dose of a macrocyclic GBCA via IP injection for longitudinal and repetitive MRI studies in small-animal models, as this approach simplifies the experimental procedure and maintains safety and image quality.

Currently, preclinical studies of nanomaterials have also achieved CE-MRI through IP administration. In one study, porous silica microparticles containing Gd chelates were intraperitoneally injected into Wistar rats and tracked in real time using MRI, demonstrating that IP administration is an effective option for nanoparticle-based imaging and treatment in laboratory animals as small as rats.¹⁶ Notably, although IP injection is manageable and safe and allows the administration of relatively large fluid volumes in small laboratory animals, strict procedures must be followed to avoid accidental intrathecal or capsular injection.¹³

This study has several limitations. First, preference for glioma lesion detection was assessed using only a limited number of paired images because of the relatively small sample size (24 mice). Second, previous studies generally used MRI scanners with field strengths above 3.0 T, whereas our study used a 3.0 T clinical MRI scanner. As a result, relatively long acquisition times were required to obtain high-resolution images with adequate SNR. However, an imaging interval of 15 min for a single route may have been too long, and the enhancement curve may not perfectly reflect the true temporal changes. Therefore, further validation using higher-field MRI systems is warranted. Third, histopathologic confirmation of tumor presence and MRI findings was not performed and will be addressed in future studies.

In conclusion, IP injection may serve as an alternative to IV GBCA administration in mice. A dose of 1 mmol/kg was appropriate for CE-MRI examinations of the mouse brain. For IV and IP administration, CE-MRI scans are recommended at 7 min and 30 min after contrast agent administration, respectively, to achieve optimal enhancement. The findings of this study provide an effective alternative route for contrast agent administration in CE-MRI examinations of small animals and may facilitate future preclinical applications involving dynamic and repetitive MRI assessment of small-animal disease models.

Supplemental Material

sj-docx-1-imr-10.1177_03000605261461956 - Supplemental material for Feasibility and optimal imaging time window for intraperitoneal versus intravenous injection of a macrocyclic gadolinium-based contrast agent in mice

Supplemental material, sj-docx-1-imr-10.1177_03000605261461956 for Feasibility and optimal imaging time window for intraperitoneal versus intravenous injection of a macrocyclic gadolinium-based contrast agent in mice by Mingyuan He, Huini Qi, Pengli Wang, Xiaojia Liu, Jianxiu Lian, Pengfei Liu and Ying Shi in Journal of International Medical Research

Supplemental Material

sj-docx-2-imr-10.1177_03000605261461956 - Supplemental material for Feasibility and optimal imaging time window for intraperitoneal versus intravenous injection of a macrocyclic gadolinium-based contrast agent in mice

Supplemental material, sj-docx-2-imr-10.1177_03000605261461956 for Feasibility and optimal imaging time window for intraperitoneal versus intravenous injection of a macrocyclic gadolinium-based contrast agent in mice by Mingyuan He, Huini Qi, Pengli Wang, Xiaojia Liu, Jianxiu Lian, Pengfei Liu and Ying Shi in Journal of International Medical Research

Footnotes

Acknowledgments

The authors acknowledge the use of a large language model (ChatGPT) for initial language proofreading and grammar checking of the manuscript. All scientific content, data analysis, interpretation, and final approval of the manuscript were performed solely by the authors.

ORCID iD

Ying Shi

Author contributions

Mingyuan He: Conceptualization, Methodology, Formal analysis, Investigation, and Writing–Original Draft. Huini Qi: Methodology and Investigation. Pengli Wang: Formal analysis and Data Curation. Xiaojia Liu: Investigation and Validation. Jianxiu Lian: Methodology and Writing–Review & Editing. Pengfei Liu: Writing–Review & Editing, Supervision, Project administration, and Funding acquisition. Ying Shi: Writing–Review & Editing, Supervision, Project administration, and Funding acquisition.

Funding

This research was funded by the project from Health Commission of Heilongjiang Province (20240909010146).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplemental material

Supplemental material for this article is available online.

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